Genetics and Frailty

Pinpointing Genes that Protect Against Frailty

August 8, 2014 - (BRONX, NY) - Frailty is a common condition associated with old age, characterized by weight loss, weakness, decreased activity level and reduced mobility, which together increase the risk of injury and death. Yet, not all elderly people become frail; some remain vigorous and robust well into old-age. The question remains: why?

“People who are frail are more vulnerable to serious complications from falls or surgery and more susceptible to infection,” said Dr. Verghese. “Understanding why some elderly people do not experience a loss of balance or strength and do not suffer from abnormal gait may help us prevent and treat such physical decline.”

The new project taps into the resources of Einstein’s LonGenity Research Study, which builds upon the Longevity Genes Project, an ongoing 15-year study with more than 500 Ashkenazi Jews over the age of 95. LonGenity compares the genetics of the centenarians and their children with those with usual survival. Over the past 10 years, Dr. Barzilai’s team has identified several biological markers that may explain their extreme longevity.

“Understanding why some elderly people do not experience a loss of balance or strength and do not suffer from abnormal gait may help us prevent and treat such physical decline.”

– Joe Verghese, M.B.B.S.

“We have shown that our centenarian participants have a significant genetic advantage over the general population. Their rare genetic variants have allowed them to live longer, healthier lives and avoid or significantly delay age-related diseases, such as Alzheimer's and type 2 diabetes,” said Dr. Barzilai,. “We now want to know if a family history of those same ‘longevity genes’ reduces the risk for frailty.”

The researchers will build on a pilot study funded by the American Federation for Aging Research that linked exceptional longevity to improved physical function and reduced risk of frailty. The Einstein team plans to further those initial efforts to identify gene variants that keep frailty at bay, explore biological pathways that may lead to frailty, and develop drugs that mimic the effect of those frailty-preventing genes.

The five-year grant, “Role of exceptional longevity genotypes in protection against frailty in aging” (R01AG044829), was awarded by the National Institute on Aging, part of the NIH.